In the treatment of a tumor, early detection is the most important. So far, for determination of the presence or absence of a tumor, a method for detecting a tumor marker, which is discharged from cancer cells into blood, has been widely applied. However, because most of the tumor markers are produced in a small amount also during the activity of normal cells, false positives are occasionally indicated due to chronic inflammation and the like. Even the carcinoembryonic antigen (CEA), which is known to have a relatively high positive rate, is associated with a false positive rate as high as 20%, leading to an assumption that in those who are determined to be positive by cancer screening, the probability of actually detecting cancer by a complete medical examination is as low as 1.5 to 4%. Further, in many cases early-stage cancer does not exhibit a high level of tumor marker, and thus detection sensitivity is insufficient. Furthermore, there are many types of cancer for which appropriate tumor markers have not yet been found, and a tumor marker capable of precisely covering all tumors is yet to be discovered. For the above reasons, there are many cases of false negatives, in which an individual suffering from early-stage cancer is inadvertently determined to be negative by cancer detection using a tumor marker, and the current situation is that the effectiveness of determination and diagnosis per se of the presence or absence of cancer using a cancer marker has come under question.
Meanwhile, it is known that administration of ALAs leads to the accumulation of protoporphyrin IX, which is a metabolite, in a tumor, which can be utilized for intraoperative diagnosis and treatment (see for example, Patent Documents 1 and 2). However, these methods have problems such as the necessity of preparing the isotypes of ALAs and mixing the body fluid collected (cells contained in the body fluid) with 5-ALA esters and exposing the resulting mixture to light.
Also, it has been previously assumed that increasing the dose of ALAs would result in improved diagnosability and therapeutic efficiency since the amount of porphyrin, which accumulates in a dependent manner, also increases. Hence, the only focus of discussion has been the escalation of dose also in the clinical field as well as in the field of basic research. However, it has been reported that because human cancer cells preferentially perform anaerobic metabolism, ALAs that are administered are accumulated in cancer cells as protoporphyrin IX, which is a precursor of heme and cytochrome (see for example, Patent Document 3).
It has been reported that tumor tissues can be clearly distinguished from normal tissues based on the amounts of uroporphyrin I and uroporphyrin III and their ratios in a sample collected after administration of ALAs (20 mg per kg of body weight), and there is also a report relating to a method for diagnosing the presence or absence of a tumor by analyzing porphyrins in a sample collected from inside or outside the body after administration of ALAs, such as urine (see for example, Patent Document 4). However, the above method has problems that it is very expensive because ALAs are administered at high concentrations, and even if formulation of ALAs is attempted, the amount of ALAs is too much to be capsulated, requiring ingestion of an intensely sour, strongly acidic aqueous solution. Moreover, administration of ALAs causes painful side effects such as vomiting and photosensitivity. Furthermore, a phenomenon in which the concentration of porphyrins increases also in a sample derived from a healthy individual, irrespective of the presence of a tumor, is also often observed. Accordingly, there is another concern that the above method has a critical problem as a diagnostic method in that although it is simple, it generates false positives.